The National Defense Research Committee (NDRC) was an organization created "to coordinate, supervise, and conduct scientific research on the problems underlying the development, production, and use of mechanisms and devices of warfare" in the United States from June 27, 1940, until June 28, 1941. Most of its work was done with the strictest secrecy, and it began research of what would become some of the most important technology during World War II, including radar and the atomic bomb. It was superseded by the Office of Scientific Research and Development in 1941, and reduced to merely an advisory organization until it was eventually terminated during 1947.

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The NDRC was created as part of the Council of National Defense, which had been created during 1916 to coordinate industry and resources for national security purposes, by an order of President Franklin Delano Roosevelt on June 27, 1940. Vannevar Bush, the director of the Carnegie Institution, had pressed for the creation of the NDRC because he had experienced during World War I the lack of cooperation between civilian scientists and the military. Bush managed to get a meeting with the President on June 12, 1940, and took a single sheet of paper describing the proposed agency. Roosevelt approved it in ten minutes. Government officials then complained that Bush was attempting to increase his authority and to bypass them — which he later admitted he was:

There were those who protested that the action of setting up NDRC was an end run, a grab by which a small company of scientists and engineers, acting outside established channels, got hold of the authority and money for the program of developing new weapons. That, in fact, is exactly what it was. (Bush 1970, p. 31–32)

In his June 15 letter which appointed Bush to the head of the committee, Roosevelt outlined that the NDRC was not meant to replace the research work done by the Army and Navy in their own laboratories or through industry contracts, but rather to "supplement this activity by extending the research base and enlisting the aid of the scientists who can effectively contribute to the more rapid improvement of important devices, and by study determine where new effort on new instrumentalities may be usefully employed." (Quoted in Stewart 1948, p. 8).

The NDRC's most important project eventually became the Manhattan Project — the full-scale project to produce nuclear weapons by the United States. An Advisory Committee on Uranium had been established to consider the feasibility of an atomic bomb as part of the National Bureau of Standards during 1939 as the result of the Einstein–Szilárd letter, but had not made significant progress. It was instructed in Roosevelt's June 15 letter to report to the NDRC and Bush, establishing the chain of command which would later result in the full-scale bomb project. During June 1940 Bush reorganized the Uranium Committee into a scientific body and eliminated military membership. No longer beholden to the military for funds, the NDRC had greater access to money for nuclear research. However, there was little impetus until the British MAUD Committee's findings were presented in 1941.

The increasing hostilities in Europe cause a desire to create a new organization which would supersede the NDRC and remedy some of the problems the NDRC was facing, in particular in converting scientific research into usable military technology ("development"), increased liaison between the different parts of military and civilian research in different government agencies, and creating a system for funding military medicine. At Bush's insistence Roosevelt issued Executive Order No. 8807 on June 28, 1941, which established the Office of Scientific Research and Development. The NDRC technically still existed after the creation of the OSRD but its authority had been reduced from being able to actually fund research to becoming simply an advisory body to the OSRD. The NDRC ceased to exist officially after its last meeting on January 20, 1947.

When it became the NDRC of the OSRD, the committee membership and structure was re-organized. The NDRC of the OSRD membership consisted of Conant (Chairman), Tolman (Vice-Chairman), Adams, Compton, and Jewett, along with the Commission of Patents (Coe until September 1945, and then Casper W. Ooms), and the representatives of the Army and Navy (which changed periodically). The Committee on Uranium was reorganized as the S-1 Section and it stopped being part of NDRC jurisdiction during December 1941.

The NDRC's research organization changed constantly during its single year of autonomous existence. During early June 1941, shortly before it was superseded by the OSRD, its organization was as follows: